Methods for production of a target substance, such as an L-amino acid, by fermentation of a microorganism have been reported. The microorganisms used for this purpose include wild-type microorganisms (wild-type strain), auxotrophic strains derived from wild-type strains, metabolic regulation mutant strains derived from wild-type strains which are resistant to various drugs, strains which act as both auxotrophic and metabolic regulation mutants, and so forth.
In recent years, recombinant DNA techniques have been used in the production of target substances by fermentation. For example, it is well-known that L-amino acid productivity of a microorganism can be improved by enhancing expression of a gene encoding an L-amino acid biosynthetic enzyme or by enhancing uptake of a carbon source to the L-amino acid biosynthesis system.
For example, known methods include, for L-lysine, enhancing expression of genes encoding enzymes such as dihydrodipicolinate synthase, aspartokinase, dihydrodipicolinate reductase, diaminopimelate decarboxylase, and diarinopimelate dehydrogenase (U.S. Pat. No. 6,040,160), reducing the activities of homoserine dehydrogenase and lysine decarboxylase (U.S. Pat. No. 5,827,698), reducing the activity of the malic enzyme (WO2005/010175), and so forth.
For L-tryptophan, desensitization to the feedback inhibition of phosphoglycerate dehydrogenase and anthranilate synthase (U.S. Pat. No. 6,180,373), deletion of tryptophanase (U.S. Pat. No. 4,371,614), and so forth are known.
For L-phenylalanine, desensitization to the feedback inhibition of chorismate mutase-prephenate dehydratase (U.S. Pat. No. 5,354,672), deletion of chorismate mutase-prephenate dehydrogenase and tyrosine repressor (WO03/044191), and so forth are known.
For L-valine, a mutant strain requiring lipoic acid for its growth and/or which is deficient in H+-ATPase (U.S. Pat. No. 5,888,783), and so forth are known. For L-leucine, desensitization to the feedback inhibition of isopropyl malate synthase (U.S. Pat. No. 6,403,342) and so forth are known, and for L-isoleucine, increasing the expression of genes encoding threonine deaminase and acetohydroxy acid synthase (U.S. Pat. No. 5,998,178), and so forth are known.
For L-serine, a strain containing 3-phosphoglycerate dehydrogenase which is desensitized to feedback inhibition by serine (U.S. Pat. No. 5,618,716), a bacterium having L-serine-producing ability and at least phosphoserine phosphatase activity, phosphoserine transaminase activity, or both, is enhanced, a bacterium deficient in L-serine decomposition ability (U.S. Pat. No. 6,037,154), a bacterium resistant to azaserine or β-(2-thienyl)-DL-alanine and having L-serine-producing ability (U.S. Pat. No. 6,258,573), and so forth are known.